Glutathione (GSH) is an antioxidant involved in several important biochemical pathways. GSH is a thiol peptide formed from three amino acids: glutamic acid, cysteine and glycine. The sulfhydryl group (—SH) of the cysteine residue in GSH provides the critical site for various conjugation and reduction reactions between GSH and other biomolecules. The oxidised dimeric form of GSH (GSSG) can be converted back to GSH through reduction by glutathione reductase. Cysteine availability is a rate-limiting factor for GSH synthesis. The term redox state is often used to describe the balance of GSH and GSSG (and other species) in a biological system such as a cell or organ. An abnormal redox state can develop in a variety of deleterious situations, such as hypoxia, shock and sepsis. Redox mechanisms also control many cellular processes. The primary role of GSH is the prevention of damage to important cellular components caused by reactive oxygen species (ROS). ROS are chemically reactive molecules containing oxygen. Examples include the hydroxyl radical (—OH), superoxide (O2−), hydrogen peroxide (H2O2), and peroxynitrite (ONOO−). During times of environmental or physiological stress, ROS levels can increase dramatically. This may result in significant damage to cell structures and is known generally as oxidative stress.
The redox state of a cell may change when the production of ROS or the availability of antioxidants changes. GSH is important in the detoxification and elimination of ROS. A reduction in cellular GSH levels can lead to ROS accumulation and oxidative stress. The regulation of GSH production is essential for cell survival in an oxidative environment.
The condition of oxidative stress is established by an imbalance between the levels or production of ROS and the ability of antioxidant defences to detoxify ROS. There is a need to keep ROS levels within a physiologically safe range and to avoid pathological tissue-damaging levels. Excessive ROS levels lead to oxidative stress which, if not adequately remediated by tissue-repair mechanisms, can cause cell injury or death. Oxidative stress plays a key role in the pathogenesis of many diseases, including cancer, inflammation, kwashiorkor (predominantly protein deficiency), seizure, autism, Down's syndrome, chronic fatigue syndrome, Alzheimer's disease, Parkinson's disease, sickle cell anaemia, liver disease, cystic fibrosis, HIV-AIDS, infection, heart attack, stroke, and diabetes. GSH therefore has an important role in reducing or preventing these diseases and associated symptoms. In addition, GSH is reported to minimise oxidative stress associated with aging, to aid tissue repair following physiological stress resulting from, for example, physical exercise and various sports, and to be beneficial for healthy fertility.
There are numerous examples of antioxidant dietary supplements available in the marketplace. Some are marketed as glutathione supplements. Others are purported to boost GSH levels. Whey protein is known to cause elevated GSH levels, and since bovine milk contains whey protein, milk can also elevate GSH levels. However, the applicant has found that beta-casein proteins, which are also found in bovine milk and the milk of other mammals, and particularly certain types of beta-caseins, are especially effective at maximising GSH levels in blood and tissue relative to other types of beta-caseins.
Milk, mainly bovine milk, consumed in populations throughout the world, is a major source of protein in human diets. Bovine milk typically comprises around 30-35 grams per litre of protein. Caseins make up the largest component (80%) of that protein, and beta-caseins make up about 37% of the caseins. In the past two decades the body of evidence implicating casein proteins, especially beta-caseins, in a number of health disorders has been growing. Beta-caseins can be categorised as A1 type beta-casein or A2 type beta-casein, depending on whether they have a proline or a histidine amino acid at position 67 of the beta-casein amino acid sequence. This difference affects the ability of the beta-casein to produce a specific heptapeptide fragment on enzymatic digestion known as BCM-7. A1 beta-casein and A2 beta-casein are the predominant beta-caseins in milk consumed in most human populations.
The applicant and others have previously determined a link between the consumption of A1 beta-casein in milk and milk products and the incidence of certain health conditions including type I diabetes (WO 1996/014577), coronary heart disease (WO 1996/036239) and neurological disorders (WO 2002/019832). Further, the applicant has shown a link between A1 beta-casein and bowel inflammation (WO 2014/193248), the symptoms of lactose intolerance (WO 2015/005804), and high blood glucose levels (WO 2015/026245).
The applicant has now found conclusive scientific evidence for a direct link between the consumption of A2 beta-casein and elevated GSH levels in blood and tissue. The applicant has therefore found a new way to treat the conditions mentioned above or to manage the symptoms of these conditions.
It is therefore an object of the invention to provide a method for improving the antioxidant capacity in an animal, or to at least provide a useful alternative to existing methods.